scholarly journals Safety and efficacy of the choline analogue SAR97276 for malaria treatment: results of two phase 2, open-label, multicenter trials in African patients

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Jana Held ◽  
Christian Supan ◽  
Carmen L. Ospina Salazar ◽  
Halidou Tinto ◽  
Léa Nadège Bonkian ◽  
...  
Keyword(s):  
Malaria Treatment ◽  
Phase 2 ◽  
Treatment Results ◽  
Open Label ◽  
Two Phase ◽  
Safety And Efficacy ◽  
Multicenter Trials ◽  
African Patients

scholarly journals Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study

2021 ◽  
Author(s):  
Takeshi Kato ◽  
Yoshinori Kagawa ◽  
Yasutoshi Kuboki ◽  
Makio Gamoh ◽  
Yoshito Komatsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Therapeutic Option ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Wild Type ◽  
Open Label ◽  
Safety And Efficacy ◽  
Multicentre Phase

Abstract Background We aimed to assess the safety and efficacy of combination treatment with panitumumab plus trifluridine/tipiracil (FTD/TPI) in patients with wild-type RAS metastatic colorectal cancer (mCRC) who were refractory/intolerant to standard therapies other than anti-epidermal growth factor receptor therapy. Methods APOLLON was an open-label, multicentre, phase 1/2 trial. In the phase 1 part, 3 + 3 de-escalation design was used to investigate the recommended phase 2 dose (RP2D); all patients in the phase 2 part received the RP2D. The primary endpoint was investigator-assessed progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and safety. Results Fifty-six patients were enrolled (phase 1, n = 7; phase 2, n = 49) at 25 Japanese centres. No dose-limiting toxicities were observed in patients receiving panitumumab (6 mg/kg every 2 weeks) plus FTD/TPI (35 mg/m2 twice daily; days 1–5 and 8–12 in a 28-day cycle), which became RP2D. PFS rate at 6 months was 33.3% (90% confidence interval [CI] 22.8–45.3). Median PFS, OS, ORR, DCR, and TTF were 5.8 months (95% CI 4.5–6.5), 14.1 months (95% CI 12.2–19.3), 37.0% (95% CI 24.3–51.3), 81.5% (95% CI 68.6–90.8), and 5.8 months (95% CI 4.29–6.21), respectively. Neutrophil count decreased (47.3%) was the most common Grade 3/4 treatment-emergent adverse event. No treatment-related deaths occurred. Conclusion Panitumumab plus FTD/TPI exhibited favourable anti-tumour activity with a manageable safety profile and may be a therapeutic option for pre-treated mCRC patients.

scholarly journals OP27 Long-term safety and efficacy of risankizumab treatment in patients with Crohn’s disease: Final results from the Phase 2 open-label extension study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S024-S025 ◽  
Author(s):  
M Ferrante ◽  
B G Feagan ◽  
J Panés ◽  
F Baert ◽  
E Louis ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Opportunistic Infections ◽  
Activity Index ◽  
Induction Treatment ◽  
Phase 2 ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension

Abstract Background Efficacy and safety of the IL-23 inhibitor risankizumab (RZB) have been assessed in patients with moderate-to-severe Crohn’s disease (CD) following induction/maintenance treatment.1,2 Responders to RZB in a Phase 2 induction/maintenance study2,3 could enrol in an open-label extension (OLE), NCT02513459.4 Final safety and efficacy results from this RZB OLE study are reported here. Methods Patients achieving clinical response (CResp) (decrease from baseline [BL] in CD Activity Index [CDAI] ≥100) without remission (CRem) (CDAI <150) after Period 2 (Week 26) or CResp/CRem after Period 3 (Week 52) of the preceding study1 received open-label 180 mg subcutaneous (SC) RZB every 8 weeks (Q8W) for up to 206 weeks. Patients who lost CResp/CRem at screening of the OLE were re-induced with open-label 600 mg IV RZB at Weeks 0, 4, and 8. Patients receiving re-induction treatment only received subsequent 180 mg SC RZB Q8W if they regained CResp/CRem following re-induction. A centrally read ileocolonoscopy was performed yearly. Treatment-emergent adverse events (AEs) were collected up to 20 weeks after the last RZB dose. CRem and endoscopic remission (ER [CD Endoscopic Index of Severity (CDEIS) ≤4 or CDEIS ≤2 for patients with isolated ileitis at BL]) were reported up to Week 152. Non-responder imputation (NRI) and observed case analysis were used for binary endpoints. Results Sixty-five patients with CD were enrolled in the OLE, with 4 patients re-induced. At BL of the preceding study, median (range) age was 34 (19–67) years and median (range) disease duration was 10 (2–38) years. Sixty patients (92%) were previously exposed to TNF antagonists. In the OLE, median (range) exposure to RZB was 1014.0 (114–1317) days. Twenty-one (32%) patients prematurely discontinued RZB, including 6 (9%) who had developed an AE. AEs were reported in 60 (92%) patients; 23 (35%) experienced serious AEs. The most common AEs were nasopharyngitis (31%), gastroenteritis (23%), and fatigue (20%). Serious infections were reported in 6 (9%) patients and opportunistic infections in 3 (5%) patients. No tuberculosis, malignancies, or deaths occurred. At Week 0 of the current study, 47 (72%) patients were in CRem and 27 (42%) patients had ER. Both CRem and ER were sustained up to Week 152 (Table). Conclusion In this final analysis of patients with CD receiving long-term open-label RZB treatment, the safety profile of RZB remained consistent with previous data² with no new safety signals. Clinical and endoscopic remissions were sustained. References

scholarly journals 669. Twelve-Month Durability of Microbiota-Based Therapy RBX2660 for Prevention of Recurrent Clostridium difficile Infection

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S306-S306
Author(s):  
Courtney Jones ◽  
Sarah Mische ◽  
Ken Blount ◽  
Bill Shannon
Keyword(s):  
Clostridium Difficile ◽  
Treatment Options ◽  
Operational Taxonomic Unit ◽  
The United States ◽  
Historical Control ◽  
Control Group ◽  
Phase 2 ◽  
Open Label ◽  
Two Phase

Abstract Background Recurrent Clostridium difficile infections (rCDI) are a public health threat with insufficient treatment options at present. Two Phase 2 clinical studies have reported the efficacy of RBX2660, a standardized, stabilized microbiota-based drug, in preventing rCDI. For one of these trials, we report herein the durability of clinical response (lack of CDI recurrence) and microbiome restoration to 12 months after RBX2660 treatment. Methods Data were drawn from an interim analysis of a multicenter, open-label Phase 2 study in which participants with multi-recurrent rCDI received up to 2 doses of RBX2660 delivered via enema 7 days apart; this analysis includes data to 12 months after treatment, with follow-up ongoing. Efficacy was defined as the absence of CDI recurrence to 56 days after the last dose; and durability is defined as a continued lack of reported recurrence. Participant stool samples collected prior to and at 1, 7, 30, 60 days and 6 and 12 months after treatment were sequenced using a shallow shotgun method, with only treatment responders reported herein. Operational taxonomic unit (OTU) data were used to calculate relative abundance at the class level and Microbiome Health Indices. Results This study included 149 RBX2660-treated participants and 110 historical control patients, in the United States and Canada. As previously reported, the efficacy of RBX2660 in preventing rCDI (79.9%; 119/149) was higher than CDI-free rates in the historical control group (51.8%, 57/110; P < 0.001). Of 109 participants who had a 6-month follow-up, 97.2% (106/109) remained CDI-free, and no new CDI recurrences were reported at 12 months. Among treatment responders, the microbiome composition was restored after treatment to predominance by Bacteroidia- and Clostridia-class bacteria, and these compositions remained stable to 12 months after treatment among participants who provided samples. Conclusion RBX2660, a microbiota-based drug, was efficacious for preventing rCDI, with clinical and microbiome restoration durability to at least 12 months after treatment. The follow-up of efficacy, safety, and microbiome restoration are ongoing. Disclosures All authors: No reported disclosures.

scholarly journals P219 Long-term safety of filgotinib in patients with PsA: week 52 safety data from a Phase 2 open-label extension study

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Laura Coates ◽  
Philip Mease ◽  
Dafna Gladman ◽  
Filip Van den Bosch ◽  
Anna Rychlewska-Hanczewska ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Safety Data ◽  
Janus Kinase ◽  
Controlled Study ◽  
Stock Ownership ◽  
Phase 2 ◽  
Open Label ◽  
Safety And Efficacy ◽  
Open Label Extension

Abstract Background Filgotinib (FIL) is an orally administered, selective janus kinase 1 (JAK1) inhibitor in development for psoriatic arthritis (PsA). Efficacy and safety of FIL in patients with active PsA were evaluated in a 16-week phase 2 study (EQUATOR, NCT03101670). After 16 weeks, patients could roll-over to an Open Label Extension (OLE) Study (EQUATOR2, NCT03320876) for the purpose of evaluating long-term safety and efficacy. The aim of this analysis was to assess safety and efficacy through 52 weeks of exposure to filgotinib. Methods Patients who completed the randomised, double-blind, placebo-controlled study were eligible for participation in the OLE, during which all patients received once daily (qd) open-label FIL 200mg. In this interim analysis of OLE, for the safety analysis, all data were included from the screening in the core study up to the data cut of 18 April 2019 in the OLE. For the efficacy analysis, all data until OLE Week 52 visit for each patient were included (observed case analysis). Results Of the 131 patients randomised and dosed in EQUATOR, 124 (95%) completed the study and 122 (93%) enrolled in EQUATOR2; 50% were female and mean age was 50. At this interim analysis, 106/122 (87%) remained in the OLE (premature discontinuations during OLE due to: 4 for safety, 11 withdrew consent, and 1 for other reasons). Cumulative patient years of exposure (PYE) on FIL were 160, median time on FIL was 66 weeks. Key safety data are summarised in Table 1. Key ≥Grade 2 treatment-emergent laboratory abnormalities seen with FIL arm (N = 128) compared with PBO (N = 66) were lymphocyte decrease 11.1% vs 4.5%, neutrophil decrease 5.5% vs 0%, ALT increase 1.6% vs 1.5% and creatinine increase 0.8% vs 0%, respectively. At week 52, 34% of the patients fulfilled criteria for minimal disease activity and 81%, 55%, and 33% of patients, respectively, achieved ACR20/50/70 responses. Conclusion FIL 200mg qd was generally well tolerated and the safety profile in PsA was comparable to that observed in the FIL rheumatoid arthritis studies. The data from this interim analysis suggest that further improvement of the patient condition can be expected beyond 16 weeks of treatment. Disclosures L. Coates: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Lilly, Novartis, Pfizer, Prothena, Sun pharma, and UCB. P. Mease: Other; Received support from Abbvie, Amgen, BMS, Celgene, Galapagos, Genentech, Gilead, Janssen, Eli Lilly, Merck, Novartis, Pfizer, SUN, and UCB. D. Gladman: Other; Received support from Abbvie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, UCB, BMS, and Galapagos. F. Van den Bosch: Other; Received support from Abbvie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, and UCB. A. Rychlewska-Hanczewska: Other; Received support from Galapagos and Gilead Sciences. C. Tasset: Corporate appointments; Employee of Galapagos NV. L. Meuleners: Corporate appointments; Employee of Galapagos NV. M. Trivedi: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Employee of Gilead Sciences, Inc... Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. R. Besuyen: Other; Employee of Galapagos NV. P. Helliwell: Other; Received support from Abbvie, Amgen, Celgene, Galapagos, Janssen, Novartis, Pfizer, and UCB.

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